Sulfoxide derivatives

The conversion of cyclic sulfides to sulfones is accompbshed by more energetic oxidations. Perhalogenated thiolanes [106] and 1,3-dithietanes [107] are oxidized to sulfones and disulfones, respectively, by a mixture of chromium trioxide and nitric acid (equation 98) The same reagent converts 2,4-dichloro-2,4-bis(tnfluoromethyl)-l,3-dif/u cto cs to disulfone derivatives [107], whereas trifluoromethaneperoxysulfonic acid converts the starting compound to a sul-fone-sulfoxide derivative [2(equation 99). 

New reactions utilizing features of sulfur atom in chiral sulfoxides, derivatives of heterocycles 99YZ126. 

Remote asymmetric induction using chiral sulfoxides, derivatives of furan, thiophene, and pyrrole 98YGK798. 

The enantiomerically pure isobomeol allyl sulfoxide derivatives (17 ,2Y,3/ ,4S )-1,7,7-tri-methyl-3-[(S)- or -(/ )-2-propenylsulfmyl]bicyclo[2.2.1]heptan-2-ol are thermally more stable inversion of configuration at sulfur, S -> / , occurs at 135-145 °C. Their lithio derivatives give exclusively y-1,4-adducts with 2-cyclopentenone19. 

TABLE 4 Specifications of Sulfoxidation-Derived Alkanesulfonates (Hostapur SAS 60)... 

TABLE 6 Specifications of Sulfoxidation-Derived Alkane-sulfonates (HCils MARLON PS 65)... 

Information is given for the sulfoxidation-derived paraffin sulfonate Marlon PS and the secondary alkanesulfonate Hostapur SAS. 

An a-fluorinated phosphinyl sulfoxide derivative, prepared as a mixture of diastereomers by the treatment of lithiated (a-fluoromethyl)diphenylphosphine oxide with menthyl p-toluenesulfinate, has been used for the preparation of enan-tiomerically pure 1-fluorovinyl and 1-fluoromethyl sulfoxides [76]. (E)-Diethyl ferf-butylsulfinylmethylphosphonate 117 has been prepared by the sulfinylation... 

Little information has appeared on derivatives of [l,2,3,5]thiatriazolopyridines as mentioned also in CHEC-11(1996) <1996CHEC-II(8)405>. In a recent study, the thermal decomposition of the sulfoxide derivative 44 in methanol in the presence of sodium triflate was investigated <1996JFC161> (Scheme 13). After a prolonged reflux, two products 2-pyridyl triflate 46a and 2-methoxypyridine 46b, was isolated in 34% and 16% yields, respectively. The authors concluded that the first step of this transformation is a thermal ring opening of 45 to a carbene intermediate. 

The pyrolytic method was first used to establish the chirality at sulfur in steroidal sulfoxide derivatives of 5a-cholestane (199). It was found that behavior of the diastereomeric sulfoxides 190, derivatives of 4/3-phenylsulfinyl-5a-cholestane having opposite configurations at sulfur, is quite different when the compounds are heated in boiling benzene. One of them, 190a, undergoes complete decomposition, affording 5a-cholest-3-ene 191, but the second diastereomer is quite inert under these conditions. 

Oxidations and Rearrangements. -Alkyl and -benzyl N,N-dlalkylthlocarbamates are converted to their sulfoxide derivatives Q) both Iri vivo in rats and on incubation with liver mlcrosomes and NADPH (3-5, 19-21). Studies with EPTC (25) reveal that they may also undergo hydroxylation at each alkyl carbon (designated by arrows) and that carbon hydroxylation at the -CH2 moiety gives an unstable intermediate which yields acetaldehyde on decomposition (19). 

Carbamylation Reactions. -Alkyl, -benzyl and -chloroallyl thiocarbamates do not readily react with GSH. In contrast, their sulfoxide derivatives ( and 6,) are very effective carbamylating agents for many thiols including GSH (19, ). The GSH conjugates formed vivo via 3 and 6 are quickly cleaved, acetylated and further metabolized as follows (19-21. 23. 24). 

One of the main research interests in this area is to find new oxidizing agents having the highest chemoselectivity to obtain the sulfoxide derivatives without overoxidation to sulfones. 1,4-Oxathiane 18 was often used as a model sulfur-containing compound to afford 82 (Table 2) and 17 similarly gave 83. m-2,6-Dimethyl-l,4-dithiane was oxidized to the... 

Chlorpromazine is 92 to 97% bound to plasma proteins, principally albumin [5,20], It crosses the blood-brain barrier, and concentrations of the drug in the brain are higher than those in plasma [17], The relationship of plasma concentration to clinical response and toxicity has not been clearly established. Chlorpromazine and its metabolites cross the placenta and are distributed into milk [21]. About 10-12 metabolites of chlorpromazine in humans have been identified. In addition to hydroxylation at positions 3 and 7 of the phenothiazine nucleus, the N-dimethylaminopropyl side chain of chlorpromazine undergoes demethylation and is metabolized to an N-oxide or sulfoxide derivative. These metabolites may be excreted as their 0-glucouronides, with small amounts of ethereal sulfates of the mono- and dihydroxy derivatives. The major metabolites found in urine are the monoglucouronide of N-demethylchlorpromazine and 7-hydroxychlorpromazine [2]. Although the plasma half life of chlorpromazine itself has been reported to be few hours, the elimination of metabolites may be very prolonged [8, 22-24]. 

Starting from optically active 1-chlorovinyl p-tolyl sulfoxide derived from 2-cyclohex-enone, the asymmetric synthesis of cyclopropane derivative (85) was realized (equation 23) . Addition reaction of lithium enolate of tert-butyl acetate to 83 gave the adduct (84) in 96% yield with over 99% ee. Treatment of the latter with i-PrMgCl in a similar way as described above afforded optically pure (15,6/ )-bicyclo[4.1.0]hept-2-ene (85) in 90% yield. 

On the other hand, when this reaction was carried out with 1-chlorovinyl p-tolyl sulfoxide derived from unsymmetrical dialkyl ketone 167 with Af-lithio 1-aminonaphthalene (entries 7 and 8), Z-ortho-alkenylated arylamine Z-171 was obtained as the main product from both vinyl sulfoxides with low stereoselectivity. The stereospecificity and stereoselectivity mentioned above are explained from the high configurational stability of the magnesium carbenoids generated from 1-chlorovinyl p-tolyl sulfoxides derived from a,/ -unsaturated ketones. 

Dithietanes, dimers of thioketones, are best stabilized by electron withdrawing groups on the ring. They are oxidized to bis-sulfoxide derivatives quite readily, and in at least one case the intermediate dioxide was isolated (Scheme 29) (80AG(E)203). 

SCHEME 32. Double homologation of alkenyl sulfoxide derivatives... 

The procedure for oxidation of the sulfide to the sulfone is based on that reported earlier by Bordwell and Pitt. The synthetic utility of phenyl vinyl sulfone and sulfoxide derives not only from their ability to serve as excellent Michael acceptors toward such reagents as enolate anions and... 

The sulfoxide derivatives of some thiabenzenes have been prepared these molecules are much more stable than the parents, and may be subjected to a wider range of reactions (Scheme 26) (74JOC3519). It is apparent that the ylidic character of these molecules is reduced vis-a-vis the non-oxygenated species. The lack of reaction with acetyl chloride should be compared with the effect of trimethylsilyl chloride in equation (72) (74JA6119). The mechanism of this reductive dealkylation has not been explored. 

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